Recent advances in IgG4-related autoimmune pancreatitis.

The incidence of IgG4-related autoimmune pancreatitis (IgG4-AIP) is high in Asia and other countries, and unnecessary treatment is often undertaken due to both missed diagnosis and misdiagnosis in clinical practice. Although IgG4-AIP has attracted increasing attention, the details of IgG4-AIP pathogenesis and systemic immune response, including its relationship to tumor pathogenesis, are still unclear. In recent years, research on serum immunological detection, pathological features, clinical manifestations, diagnosis and treatment measures for IgG4-AIP has gradually increased. It is of great importance to summarize and discuss the latest progress regarding IgG4-AIP disease.

Glucose metabolism-based signature predicts prognosis and immunotherapy strategies for colon adenocarcinoma.

BACKGROUND: The global prevalence and metastasis rates of colon adenocarcinoma (COAD) are high, and therapeutic success is limited. Although previous research has primarily explored changes in gene phenotypes, the incidence rate of COAD remains unchanged. Metabolic reprogramming is a crucial aspect of cancer research and therapy. The present study aims to develop cluster and polygenic risk prediction models for COAD based on glucose metabolism pathways to assess the survival status of patients and potentially identify novel immunotherapy strategies and related therapeutic targets. METHODS: COAD-specific data (including clinicopathological information and gene expression profiles) were sourced from The Cancer Genome Atlas (TCGA) and two Gene Expression Omnibus (GEO) datasets (GSE33113 and GSE39582). Gene sets related to glucose metabolism were obtained from the MSigDB database. The Gene Set Variation Analysis (GSVA) method was utilized to calculate pathway scores for glucose metabolism. The hclust function in R, part of the Pheatmap package, was used to establish a clustering system. The mutation characteristics of identified clusters were assessed via MOVICS software, and differentially expressed genes (DEGs) were filtered using limma software. Signature analysis was performed using the least absolute shrinkage and selection operator (LASSO) method. Survival curves, survival receiver operating characteristic (ROC) curves and multivariate Cox regression were analyzed to assess the efficacy and accuracy of the signature for prognostic prediction. The pRRophetic program was employed to predict drug sensitivity, with data sourced from the Genomics of Drug Sensitivity in Cancer (GDSC) database. RESULTS: Four COAD subgroups (i.e., C1, C2, C3 and C4) were identified based on glucose metabolism, with the C4 group having higher survival rates. These four clusters were bifurcated into a new Clust2 system (C1 + C2 + C3 and C4). In total, 2175 DEGs were obtained (C1 + C2 + C3 vs. C4), from which 139 prognosis-related genes were identified. ROC curves predicting 1-, 3- and 5-year survival based on a signature containing nine genes showed an area under the curve greater than 0.7. Meanwhile, the study also found this feature to be an important predictor of prognosis in COAD and accordingly assessed the risk score, with higher risk scores being associated with a worse prognosis. The high-risk and low-risk groups responded differently to immunotherapy and chemotherapeutic agents, and there were differences in functional enrichment pathways. CONCLUSIONS: This unique signature based on glucose metabolism may potentially provide a basis for predicting patient prognosis, biological characteristics and more effective immunotherapy strategies for COAD.

Prediction and therapeutic targeting of the tumor microenvironment-associated gene CTSK in gastric cancer.

BACKGROUND: Cathepsin-K (CTSK) is overexpressed in Gastric cancer (GC) and the mechanism of its overexpression in GC is still unclear. The present work found CTSK as a potential predictive biomarker and immunotherapeutic target for GC based on the tumor microenvironment (TME). METHODS: From public databases, gene expression profiles and clinical data of GC were downloaded to analyze the distribution of stromal and immune cells and tumor abundance in TME. Differentially expressed genes (DEGs) associated with TME were obtained by differential analysis, followed by cross-screening to obtain CTSK as a gene associated with TME. Next, a series of methods and tools were employed to explore the relationships between clinicopathological features of GC and CTSK expression as well as prognosis, tumor immune microenvironment, immune checkpoints and drug sensitivity. And GSEA was used to investigate the potential role of CTSK in the tumor microenvironment of GC. RESULTS: From the dataset, we obtained a total of 656 DEGs associated with TME and the stromal component of TME was found to be closely involved in GC prognosis. CTSK was cross-screened as the key gene associated with TME by the PPI network and univariate Cox regression analysis. Pan-cancer analysis revealed significant high expression of CTSK in a variety of cancers. Subsequently, we hypothesized that high-expressed CTSK was closely correlated with poor prognosis and lymph node metastasis of tumors, and that CTSK, a GC TME-related gene, was largely involved in a range of biological behaviors of tumors, with a significant correlation between several immune cells. CONCLUSION: CTSK was validated as a potential prognostic biomarker related to TME of GC and could be a promising next-generation immunotherapeutic target for GC.

Different 18F-FDG imaging: A rare case of liver multiple carcinomas.

A 49-year-old man was referred to the hospital with the complaints of haematochezia and weight loss. Colonoscopy and pathological needle biopsy suggested moderately to highly differentiated adenocarcinoma. The patient underwent abdominal CT examination, which demonstrated two augmented and irregular masses in the liver. However, the glucose metabolism of 18F-FDG in these two lesions was completely different. Considering the different glucose metabolism, a needle biopsy of the liver mass was performed, and the diagnosis was rectal cancer with liver metastasis and primary hepatocellular carcinoma.

Evidence of a Relationship Between Plasma Leptin, Not Nesfatin-1, and Craving in Male Alcohol-Dependent Patients After Abstinence.

The goal of this study was to determine whether the plasma leptin, nesfatin-1, cortisol, brain-derived neurotrophic factor (BDNF), and inflammatory cytokines could be used as potential biomarkers for the degree of craving in the alcohol-dependent patients after 1 month of abstinence. A total of 83 patients with alcohol use disorder (AUD) and 61 healthy subjects were assessed. Patients with AUD were selected from Department of Material Dependence, Anhui Mental Health Center, and subjects in the control group were selected from healthy volunteers. The Alcohol Urge questionnaire Scale (AUQ) was used to evaluate the extent of craving for alcohol, and the Michigan Alcoholism Screening Test (MAST), the Fagerstrom Test for Nicotine Dependence (FTND), the Self-Rating Anxiety Scale (SAS), and the Self-Rating Depression Scale (SDS) were also assessed in patients with AUD. Enzyme-Linked Immunosorbent Assay (ELISA) was used for the measurement of plasma leptin, nesfatin-1, cortisol, BDNF, Interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) levels. Compare with healthy controls, the average leptin, leptin/BMI, IL-6, CRP, and TNF-α levels in patients with AUD were significantly increased, while the BDNF levels were significantly decreased. Moreover, the partial correlational analysis showed that the AUQ scores of the alcohol-dependent patients were positively correlated with the plasma leptin levels (r = 0.613, P < 0.001), rather than nesfatin-1 (r = 0.066, P = 0.569) after controlling for age as covariate. Furthermore, plasma nesfatin-1 levels were found to be correlated with the SDS scores (r = 0.366, P = 0.001) in the AUD group. In addition, plasma leptin levels were positively associated with the plasma IL-6 (r = 0.257, P = 0.033), CRP (r = 0.305, P = 0.011), and TNF-α (r = 0.311, P = 0.009) levels, and negatively associated with the BDNF levels (r = -0.245, P = 0.042) in patients with AUD. These results suggest that plasma leptin, but not nesfatin-1, might be a potential biomarker for the degree of craving in alcohol-dependent patients after 1 month of abstinence, the mechanism of which might be related to the dysfunction of the inflammatory cytokines and BDNF levels.

Up-regulation of miR-155 contributes to TNF-mediated hepatocyte apoptosis in acute liver failure.

BACKGROUND/AIMS: Acute liver failure (ALF) is due to severe immune response, resulting in massive apoptosis/necrosis of hepatocytes. The precise mechanism has not been explored yet. MATERIALS AND METHODS: The mouse with ALF model was induced by D-GalN/LPS; the hepatic miRNAs expression profile was evaluated by miRNA microarray and verified by RT-PCR. During the ALF in mice, the miR-155 expression was detected in the liver as well as in spleen. Then the correlation between miR-155 and inflammatory cytokines was evaluated. Furthermore, the miR-155 expression in activated Raw264.7 cells and apoptotic hepatocytes was also studied. Finally, the regulatory roles of miR-155 in TNF expression of apoptotic hepatocytes were shown. RESULTS: It was shown that miRNAs changed in the mice with ALF relating to hepatocytes apoptosis/necrosis; the selected miRNAs were confirmed with RT-PCR. miR-155 was up-regulated, but miR-698, -720, and -329 were down-regulated. Moreover, hepatic miR-155 was up-regulated at all-time points in the liver, but only at 7 h in spleen of mice with ALF. A significant correlation was observed between hepatic miR-155 and TNF/IL-6 in mice with ALF, which was supported by the findings in vitro showing up-regulated miR-155 in Raw264.7 cells and Hepa1-6 cells under LPS or D-GalN+TNF induction, respectively. Moreover, a correlation was observed between miR155 and TNF levels in vivo and in vitro. CONCLUSION: These data demonstrate that miR-155 regulates TNF-mediated hepatocyte apoptosis in ALF, which provides some useful information in both basic and clinical researches.

Nesfatin-1 and cortisol: potential novel diagnostic biomarkers in moderate and severe depressive disorder.

BACKGROUND: This study aimed to determine whether plasma nesfatin-1, cortisol, and inflammatory cytokines could be used as novel noninvasive biomarkers for the diagnosis of moderate and severe depressive disorder (MSDD). MATERIALS AND METHODS: A total of 70 patients with MSDD and 70 healthy subjects were assessed. Patients with MSDD were selected from Hefei Fourth People's Hospital, Anhui Mental Health Center, and subjects in the control group were selected from healthy volunteers. Hamilton Depression Rating Scale-17 (HAMD-17) was used to evaluate the two groups. ELISA was used for the measurement of plasma nesfatin-1, cortisol, IL-6, C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) levels. The diagnostic value of plasma nesfatin-1, cortisol, IL-6, CRP, and TNF-α for MSDD was assessed. RESULTS: Compared to healthy controls, the HAMD-17 scores and average nesfatin-1, cortisol, IL-6, and CRP levels in patients with MSDD were significantly increased. Moreover, multivariate linear regression analysis showed that HAMD-17 score was positively associated with plasma nesfatin-1 and cortisol. Furthermore, the results of the receiver operating characteristic (ROC) curve analysis revealed an area under curve (AUC) of 0.985 with 94.3% sensitivity and 97.1% specificity of nesfatin-1, and an AUC of 0.957 with 91.4% sensitivity and 85.7% specificity of cortisol in discriminating patients with MSDD from healthy volunteers. A combined ROC analysis using nesfatin-1 and cortisol revealed an AUC of 0.993 with a sensitivity of 97.1% and a specificity of 98.6% in separating patients with MSDD from healthy volunteers. CONCLUSION: These results suggest that plasma nesfatin-1 and cortisol might be potential novel biomarkers for the diagnosis of MSDD.